GLP-1 receptor agonists probably reduced all-cause death and major cardiovascular events in people with chronic kidney disease and diabetes (based on 4 studies with 6,292 participants).
Systematic Review (n=6,292)
Do GLP-1 receptor agonists reduce death, MACE, and kidney failure in people with chronic kidney disease and diabetes?
In patients with diabetes and CKD, GLP-1 receptor agonists probably reduce all-cause mortality and major cardiovascular events, though effects on kidney failure and cardiovascular death are less certain.
BACKGROUND: Approximately 40% of people with diabetes develop kidney failure and experience an accelerated risk of cardiovascular complications. Glucagon-like peptide 1 (GLP-1) receptor agonists are glucose-lowering agents that manage glucose and weight control. OBJECTIVES: We assessed the benefits and harms of GLP-1 receptor agonists in people with chronic kidney disease (CKD) and diabetes. SEARCH METHODS: The Cochrane Kidney and Transplant Register of Studies was searched to 10 September 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled studies were eligible if participants with diabetes and CKD were randomly allocated to a GLP-1 receptor agonist, placebo, standard care or a second glucose-lowering agent. CKD included all stages (from 1 to 5). DATA COLLECTION AND ANALYSIS: Three authors independently extracted data and assessed the risk of bias using the risk of bias assessment tool 2. Pooled analyses using summary estimates of effects were obtained using a random-effects model, and results were expressed as risk ratios (RR) and/or hazard ratio (HR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. The primary outcomes included death (all-cause and cardiovascular), 3- and 4-point major adverse cardiovascular events (MACE), kidney failure, composite kidney outcome, and severe hypoglycaemia. The secondary outcomes included non-fatal or fatal myocardial infarction (MI) or stroke, non-fatal peripheral arterial events, heart failure, hospitalisation due to heart failure, estimated glomerular filtration rate or creatinine clearance, doubling of serum creatinine, urine albumin-to-creatinine ratio, albuminuria progression, vascular access outcomes, body weight, body mass index, fatigue, life participation, peritoneal dialysis infection, peritoneal dialysis failure, adverse events, serious adverse events, withdrawal due to adverse events, HbA1c, sudden death, acute MI, ischaemic stroke, and coronary revascularisation. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: = 44%; 4 studies, 6,292 participants; low-certainty evidence). The effects of GLP-1 receptor agonists compared to standard care or other hypoglycaemic agents were uncertain. No studies evaluated treatment on risks of fatigue, life participation, amputation or fracture. AUTHORS' CONCLUSIONS: GLP-1 receptor agonists probably reduced all-cause death but may have little or no effect on cardiovascular death in people with CKD and diabetes. GLP-1 receptor agonists probably lower major cardiovascular events, probably have little or no effect on kidney failure and composite kidney outcomes, and may have little or no effect on the risk of severe hypoglycaemia in people with CKD and diabetes.
Natale et al. (Tue,) conducted a systematic review in Chronic kidney disease and diabetes (n=6,292). GLP-1 receptor agonists vs. Placebo, standard care, or a second glucose-lowering agent was evaluated on Death (all-cause and cardiovascular), 3- and 4-point major adverse cardiovascular events (MACE), kidney failure, composite kidney outcome, and severe hypoglycaemia. GLP-1 receptor agonists probably reduced all-cause death and major cardiovascular events in people with chronic kidney disease and diabetes (based on 4 studies with 6,292 participants).